👤 Shabana

To measure the expression level of the vacuolar protein sorting 13 (VPS13) gene and stimulator of interferon genes (STING) in patients with SLE with and without reported neuropsychiatric symptoms to establish their possible role in the pathogenesis of neuropsychiatric SLE (NPSLE). This study included 100 subjects: 50 patients diagnosed with SLE and 50 age-matched and sex-matched healthy participants as the control group. The patients with SLE were further subdivided into NPSLE and non-NPSLE groups. All the subjects underwent rheumatological, neurological and psychological evaluation, MRI, VPS13C gene and STING expression assessment via quantitative real-time PCR. Seventy-eight per cent of the SLE group were classified as non-NPSLE, and 22% were classified as NPSLE. Positive MRI results were found in 55% of the patients with NPSLE and 7.7% of the patients without NPSLE.VPS13C expression levels were decreased in the patients with SLE compared with the control (p<0.001), while STING expression levels showed higher levels in the patients in comparison with the control (p<0.001). Both markers showed significant differences between the MRI-positive and MRI-negative groups.At a cut-off value of 0.225 for the VPS13C assessment and a cut-off value of 3.15 for STING expression, both markers were able to distinguish patients with NPSLE from those who were non-NPSLE; however, VPS13C performed better. The VPS13C expression levels were decreased in patients with NPSLE compared with patients without NPSLE, while STING expression levels showed higher levels in NPSLE. Both were associated with the MRI findings. To distinguish patients with NPSLE from those without it, the VPS13C assessment performed better. Show less

Ventricular septal defects (VSDs) are one of the leading causes of death due to cardiac anomalies during the first months of life. The prevalence of VSD in neonates is reported up to 4%. Despite the remarkable progress in medication, treatment and surgical procedure for VSDs, the genetic etiology of VSDs is still in infancy because of the complex genetic and environmental interactions. Three hundred fifty subjects (200 VSD children and 150 healthy controls) were recruited from different pediatric cardiac units. Pediatric clinical and demographic data were collected. A total of six variants, rs1017 (ISL1), rs7240256 (NFATc1), rs36208048 (VEGF), variant of HEY2, rs11067075 (TBX5) and rs1801133 (MTHFR) genes were genotyped by tetra-ARMS PCR and PCR-RFLP methods. The results showed that in cases, the rs1017 (g.16138A > T) variant in the ISL1 gene has an allele frequency of 0.42 and 0.58 respectively for the T and A alleles, and 0.75 and 0.25 respectively in the controls. The frequencies of the AA, TA and TT genotypes were, 52%, 11% and 37% in cases versus 21%, 8% and 71% respectively in the controls. For the NFATc1 variant rs7240256, minor allele frequency (MAF) was 0.43 in cases while 0.23 in controls. For the variant in the VEGF gene, genotype frequencies were 0% (A), 32% (CA) and 68% (CC) in cases and 0.0%, 33% and 67% respectively in controls. The allele frequency of C and A were 0.84 and 0.16 in cases and 0.83 and 0.17 respectively in controls. The TBX5 polymorphism rs11067075 (g.51682G > T) had an allelic frequency of 0.44 and 0.56 respectively for T and G alleles in cases, versus 0.26 and 0.74 in the controls. We did not detect the presence of the HEY2 gene variant (g.126117350A > C) in our pediatric cohort. For the rs1801133 (g.14783C > T) variant in the MTHFR gene, the genotype frequencies were 25% (CC), 62% (CT) and 13% (TT) in cases, versus 88%, 10% and 2% in controls. The ISL1, NFATc1, TBX5 and MTHFR variants were found to be in association with VSD in the Pakistani pediatric cohort whilst the VEGF and HEY2 variants were completely absent in our cohort. We propose that a wider programme of genetic screening of the Pakistani population for genetic markers in heart development genes would be helpful in reducing the risk of VSDs. Show less

Conventional coronary artery disease (CAD) risk factors like age, gender, blood lipids, hypertension and smoking have been the basis of CAD risk prediction algorithms, but provide only modest discrimination. Genetic risk score (GRS) may provide improved discrimination over and above conventional risk factors. Here we analyzed the genetic risk of CAD in subjects from Pakistan, using a GRS of 21 variants in 18 genes and examined whether the GRS is associated with blood lipid levels. 625 (405 cases and 220 controls) subjects were genotyped for variants, NOS3 rs1799983, SMAD3 rs17228212, APOB rs1042031, LPA rs3798220, LPA rs10455872, SORT1 rs646776, APOE rs429358, GLUL rs10911021, FTO rs9939609, MIA3 rs17465637, CDKN2Ars10757274, DAB2IP rs7025486, CXCL12 rs1746048, ACE rs4341, APOA5 rs662799, CETP rs708272, MRAS rs9818870, LPL rs328, LPL rs1801177, PCSK9 rs11591147 and APOE rs7412 by TaqMan and KASPar allele discrimination techniques. Individually, the single SNPs were not associated with CAD except APOB rs1042031 and FTO rs993969 (p = 0.01 and 0.009 respectively). However, the combined GRS of 21 SNPs was significantly higher in cases than controls (19.37 ± 2.56 vs. 18.47 ± 2.45, p = 2.9 × 10 The GRS was quantitatively associated with CAD risk and showed association with blood lipid levels, suggesting that the mechanism of these variants is likely to be, in part at least, through creating an atherogenic lipid profile in subjects carrying high numbers of risk alleles. Show less

Serum Triglyceride (TG) and High Density Lipoprotein (HDL-C) levels are modifiable coronary artery disease (CAD) risk factors. Polymorphisms in the genes regulating TG and HDL-C levels contribute to the development of CAD. The objective of the current study was to investigate the effect of four such single nucleotide polymorphism (SNPs) in the genes for Lipoprotein Lipase (LPL) (rs328, rs1801177), Apolipoprotein A5 (APOA5) (rs66279) and Cholesteryl ester transfer protein (CETP) (rs708272) on HDL-C and TG levels and to examine the association of these SNPs with CAD risk. A total of 640 subjects (415 cases, 225 controls) were enrolled in the study. The SNPs were genotyped by KASPar allelic discrimination technique. Serum HDL-C and TG were determined by spectrophotometric methods. The population under study was in Hardy Weinberg equilibrium and minor allele of SNP rs1801177 was completely absent in the studied subjects. The SNPs were association with TG and HDL-C levels was checked through regression analysis. For rs328, the effect size of each risk allele on TG and HDL-C (mmol/l) was 0.16(0.08) and -0.11(0.05) respectively. Similarly, the effect size of rs662799 for TG and HDL-C was 0.12(0.06) and -0.13(0.0.3) and that of rs708272 was 0.08(0.04) and 0.1(0.03) respectively. The risk allele frequencies of the SNPs were higher in cases than controls, but the difference was not significant (p > 0.05) and SNPs were not associated with CAD risk (p > 0.05). The combined gene score of four SNPs significantly raised TG and lowered HDL-C but did not increase CAD risk. The studied SNPs were associated with TG and HDL-C levels, but not with CAD in Pakistani population under study. Show less